Drug-resistance mutation of microorganisms reflects structure and function changes of the ribosome and RNA polymerase.These changes can have significant effects on secondary metabolism in the mutant strain.Thus,ribosome engineering is an effective approach to develop mutant strains that overproduce secondary metabolites(i.e.antibiotics) by screening various drug-resistance mutations.We introduced the concept and the mechanisms of the ribosome engineering.The efficacy of the strain improvement was highlighted in Streptomyces spp.by introducing combinatory drug-resistances.The applications of the method in the strain-breeding of various bacteria were also summarized.